Regulation of Depression

Depression is known to have many symptoms, among them anhedonia and hopelessness. While it is known that these symptoms lie in a web of complex circuits, Tye et. Al. and Chaudhury et. Al. focus their research on one specific circuit known to be involved in reward and motivation- the pathway of dopamine neurons from the ventral tegmental area to the nucleus accumbens. After reading both papers, it seems that both authors agree on the bidirectional control of dopamine neurons. Taking this feature of DA neurons in mind, both papers use optogenetics to observe the effects of inhibiting and stimulating the neurons and interpret how this can be correlated to depressive symptoms.

Tye and Chaudhury both used optogenetics to stimulate dopamine neurons in the ventral tegmental area, but their results are stark in contrast. Tye found that stimulating neurons using phasic illumination reduced stress induced depressive symptoms. In the tail suspension test, activation of neurons in rats exposed to chronic mild stress brought the rats up to the level of rats that did not receive the chronic mild stress. Chaudhury found that stimulation of the dopamine neurons during a social interaction test induced “susceptible” phenotype, or caused more depressive symptoms, opposite of Tye.

I found it interesting that in Tye’s paper, increased firing of VTA dopamine neurons caused an increase in sucrose preference in stressed mice, while in Chaudbury’s paper, increased firing of VTA dopamine neurons caused a decrease in sucrose preference. Chaudbury emphasized the difference in the effects of tonic and phasic firing, but both of these instances involved phasic firing.

As Tye mentions at the end of the paper, the contrasting findings may be due to the different types of stress that both papers were measuring. Tye subjected the mice to chronic mild stress and then measured data using the tail suspension test, and the sucrose preference test while Chaudhury subjected mice to a social defeat paradigm. The social defeat paradigm induces a high stress situation, in which the mouse is physically attacked, while chronic mild stress is more of a build up of tiny stressors over time. It makes sense that the brain would handle these different stressful situations through different circuits. These two papers compliment each other in illustrating the varying levels of stress induced depression. Since each case of depression is so different, I think understanding the circuitry behind different levels of stress could lead to more personalized and effective drug treatments.